title: Combined mutations in pre-s/surface and core promoter/precore regions of hepatitis B virus increase the risk of hepatocellular carcinoma: a case-control study.
abstract: BACKGROUND
  We sought to investigate the role of sequence variations in pre-S/surface and basal core promoter (BCP)/precore regions of the hepatitis B virus (HBV) in hepatocellular carcinoma (HCC).
  
  
  METHODS
  The direct sequencing in pre-S/surface and BCP/precore regions of HBV was determined for 80 patients with HCC and 160 control patients with HBV infection.
  
  
  RESULTS
  Compared with control patients, patients with HCC had higher frequencies of pre-S deletions and amino acid substitutions at codon 4, 7, and 81 in pre-S1 genes; at the start codon in pre-S2 genes; and at codon 68 in surface genes. Patients also had a lower frequency of amino acid substitution at codon 2 in pre-S2 genes, compared with control patients. In BCP/precore regions, patients with HCC had higher frequencies of C or G1753, A1762/T1764, T1846, and A1899. Multivariate analysis showed that pre-S deletions, I68T surface gene, T1762/A1764, and A1899 were independent factors associated with the development of HCC. The HBV strain with a complex mutation pattern rather than a single mutation was associated with HCC, and the HCC risks increased for patients having these factors in combination.
  
  
  CONCLUSIONS
  Pre-S deletions, I68T in surface gene, T1762/A1764, and A1899 were independent risk factors for HCC. Combination of these viral mutations appeared to increase the risk of HCC.
authors.affiliation: Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, 123 Ta Pei Road, Kaohsiung, Taiwan.
authors.forename: Chien-Hung
authors.initials: CH
authors.lastname: Chen
authors.forename: Chi-Sin
authors.initials: CS
authors.lastname: Changchien
authors.forename: Chuan-Mo
authors.initials: CM
authors.lastname: Lee
authors.forename: Chao-Hung
authors.initials: CH
authors.lastname: Hung
authors.forename: Tsung-Hui
authors.initials: TH
authors.lastname: Hu
authors.forename: Jing-Houng
authors.initials: JH
authors.lastname: Wang
authors.forename: Jyh-Chwan
authors.initials: JC
authors.lastname: Wang
authors.forename: Sheng-Nan
authors.initials: SN
authors.lastname: Lu
mesh_terms: D000328:Adult; D006528:Carcinoma, Hepatocellular / Q000209:etiology* / Q000821:virology; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D006509:Hepatitis B / Q000150:complications* / Q000821:virology*; D006514:Hepatitis B Surface Antigens / Q000235:genetics*; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D011401:Promoter Regions, Genetic / Q000235:genetics; D012307:Risk Factors
chemical_list: D006514:Hepatitis B Surface Antigens